L'infezione tubercolare nel bambino: il contributo dei nuovi test immunologici

Negli ultimi decenni si \ue8 verificato un incremento dei casi di tubercolosi anche in aree tradizionalmente ritenute a bassa prevalenza di malattia, in particolare tra i giovani adulti recentemente immigrati. Questo fattore rappresenta un rischio di maggiore diffusione dell\u2019infezione tra i bambini. I soggetti in et\ue0 pediatrica, in particolare quelli al di sotto dei 5 anni di et\ue0, rappresentano un gruppo ad alto rischio di sviluppare malattia se infettati dal M. tuberculosis; peraltro, la diagnosi in questo gruppo di et\ue0 presenta notevoli difficolt\ue0 per l\u2019aspecificit\ue0 del quadro clinico-radiologico e la bassa resa dei test microbiologici. I bambini ed i ragazzi a rischio di infezione tubercolare latente devono essere pertanto precocemente individuati ed opportunamente trattati.Fino a pochi decenni orsono l\u2019unico test disponibile per individuare i soggetti con infezione tubercolare latente era il test cutaneo tubercolinico (o test di Mantoux), che per\uf2 presenta notevoli limiti, in particolare mostra scarsa sensibilit\ue0 (nei pazienti immunodepressi) e scarsa specificit\ue0 (nei soggetti vaccinati con BCG). Sono stati recentemente sviluppati test basati sul rilascio di interferon-gamma che hanno dimostrato di avere buona sensibilit\ue0 ed elevata specificit\ue0 anche nei grupi pi\uf9 a rischio. \uc8 prevedibile quindi che l\u2019applicazione di questi nuovi diagnostici in ambito pediatrico possa contribuire ad una pi\uf9 accurata individuazione dei soggetti con infezione tubercolare contribuendo quindi a ridurre la diffusione della malattia nella popolazione generale

Clinical characterization of neonatal and pediatric enteroviral infections: an Italian single center study

Enteroviruses (EVs) are an important cause of illness, especially in neonates and young infants. Clinical and laboratory findings at different ages, brain imaging, and outcomes have been inadequately investigated.Background Enteroviruses (EVs) are an important cause of illness, especially in neonates and young infants. Clinical and laboratory findings at different ages, brain imaging, and outcomes have been inadequately investigated. Methods We retrospectively investigated EV infections occurring at an Italian tertiary care center during 2006-2017. Cases were confirmed with a positive polymerase chain reaction on blood or cerebrospinal fluid. Clinical and laboratory findings according to age at presentation were analyzed. Results Among 61 cases of EV infection, 56 had meningitis, 4 had encephalitis, and 1 had unspecific febrile illness. Forty-seven cases (77.0%) presented at less than 1 year of age, and most were less than 90 days of age (n = 44). Presentation with fever (p < 0.01), higher median temperature (p < 0.01), and irritability (p < 0.01) were significantly more common among infants aged less than 90 days, who also had significantly higher peak temperatures during the course of the disease (p < 0.01). In contrast, gastrointestinal symptoms were more common in infants and children aged over 90 days (p = 0.02). Only 4 of 61 infections (6.5%) were severe and all affected younger infants (p < 0.01). Conclusions We detail epidemiological, clinical, and laboratory findings in a cohort of 61 children. Infants aged less than 90 days have more severe disease; they are more likely to present with fever, higher median temperature, and irritability and less likely to develop gastrointestinal symptoms

Once-daily intrapleural urokinase treatment of complicated parapneumonic effusion in pediatric patients

In this paper, we describe our experience in the treatment of childhood empyema using urokinase. Patients' ages ranged from 2 to 12 years. Urokinase (dosage: 3,100 IU/kg/day) was diluted in normal saline to produce 1000 IU/ml (maximum dosage 100,000 IU in 100 ml of normal saline). After 2 hours, the clamped catheters were released and connected to water-seal suction at a negative pressure of 10 cm H2O. Pleural irrigations were continued once a day until thoracostomy tube output decreased to less than 10 ml/day (urokinase treatment mean duration: 11.5 days). The complete resolution of the chest effusion was assessed on chest ultrasound scan and radiographs. None of the patients experienced any side effects due to urokinase. It would now seem reasonable to advocate small chest tube thoracostomy and intrapleural urokinase as first-line treatment of pleural empyema in children, with surgery indicated as a secondaryintervention

rates of latent tuberculosis infection using different diagnostica test

Background.The interferon−g−release assays (IGRA) are emerging as an attractive alternative to the tuberculin skin test (TST) for the diagnosis of latent tuberculosis infection (LTBI).The absence of a gold standard for LTBI hampers the assessment of any diagnostic test. Methods.In a prospective study,229 patients (mean age 35.5±24.6 y) from different ward of the Hospital (Respiratory Diseases,Dermatology, Rheumatology, Pediatrics, Infectious Diseases, Hematology and Transplant Unit) were simultaneously tested for a suspect of either LTBI or active tuberculosis using all commercially available diagnostics: TST,QuantiFERON−TB Gold (QFT−2G), QuantiFERON−TB Gold In−Tube(QFT−3G) and T−SPOT.TB(TS.TB). Results. 42(18.3%),37(16.2%),59(25.8%) and 79(34.5%) patients were positive with TST,QFT−2G,QFT−3G and TS.TB, respectively.TS.TB(p<0.001) and QFT−3G(p=0.016) provided more positive results than TST, while no difference was found for TST and QFT−2G(p=0.53).All IGRA showed a good overall agreement (TS.TB vs QFT−2G,k=0.55; TS.TB vs QFT−3G,k=0.72;QFT−2G vs QFT−3G, k=0.62). In 22 subjects (9.6%) QFT−3G was positive and QFT−2G negative. Indeterminate results were more frequent with QFT−2G(18.3%) and QFT−3G (12.7%) than with TS.TB(1.3%,p<0.0001). Conclusion. Rates of LTBI as detected by different diagnostic tests may have significant variations. Performances of various IGRA formats were variable in this population

Performance of commerical blood tests for the diagnosis of latent tuberculosis infection in children and adolescents

BACKGROUND: The accurate diagnosis of latent tuberculosis infection reduces the risk of progression to severe disseminated disease. However, in young children, a major limitation of the standard tuberculin skin test is that false-negative results cannot be detected. The new interferon-gamma release assays QuantiFERON-TB Gold (Cellestis Carnegie Victoria, Australia), QuantiFERON-TB In-Tube (Cellestis), and T-SPOT.TB (Oxford Immunotec, Abingdon, United Kingdom) show promise of greater accuracy, but they may also be affected by impaired cellular immunity, resulting in indeterminate results (ie, insufficient response in positive-control wells).OBJECTIVE:To evaluate the impact of age on the performance of interferon-gamma release assays when used in a routine hospital setting among children tested for suspected active or latent TB infection.METHODS:We retrospectively studied 496 children 0 to 19 years of age who had been tested with the tuberculin skin test and at least 1 interferon-gamma release assay: 181 with QuantiFERON-TB Gold and 315 with QuantiFERON-TB In-Tube. In 154 of the children, paired interferon-gamma release assay testing was available: 87 with QuantiFERON-TB Gold/T-SPOT.TB and 67 with QuantiFERON-TB In-Tube/T-SPOT.TB.RESULTS:Compared with T-SPOT.TB, the rates of indeterminate results were significantly higher for both QuantiFERON-TB Gold and QuantiFERON-TB In-Tube. QuantiFERON-TB Gold and QuantiFERON-TB In-Tube also gave indeterminate results more frequently in children /=4 years of age. Indeterminate results were associated with younger age for both QuantiFERON-TB Gold and QuantiFERON-TB In-Tube but not for T-SPOT.TB. Considering age as a binary variable (/=4 years of age), a significantly higher concentration of phytohaemagglutinin-produced interferon-gamma was observed in older children with both QuantiFERON-TB Gold and QuantiFERON-TB In-Tube.CONCLUSIONS:Different blood tests for the diagnosis of latent tuberculosis infection in children seem to perform differently, because both QuantiFERON-TB tests were more likely than T-SPOT.TB to give indeterminate results in children <4 years of age

The steroid-sparing effect of JAK inhibitors across multiple patient populations

IntroductionJAK-inhibitors (JAK-i) represent an effective treatment in Rheumatoid Arthritis (RA) and Psoriatic Arthritis (PsA). Oral glucocorticoids (OGC) are commonly used in combination with JAK-i to reach therapeutic target. We aimed to assess, in a real-life setting, the reduction of OGC dose during JAK-i treatment in active RA and PsA patients. MethodsWe prospectively enrolled 103 patients (88 RA, 15 PsA) treated with JAK-i: 24% bio-naïve (b-naïve), 76% bDMARD-insufficient responders (bDMARD-IR) and 40% difficult to treat (D2T), defined as failure of ≥2 bDMARDs with different mechanism of action. Disease activity (DAS28 and DAPSA, VAS-pain, GH) and OGC dose was collected at baseline and after 3, 6 and 12 months (T3, T6, T12) of treatment.ResultsIn all the cohort and in b-naïve patients we reported a reduction of OGC dose at all time-points; bDMARD-IR patients were able to reduce OGC dose at T3 and T12; D2T ones only at T3. We reported an improvement of disease activity and withdrawal of OGC as early as three months of therapy, at all time-points, regardless of line of bDMARD treatment. ConclusionChronic OGC may cause detrimental bone, metabolic, cardiovascular side effects and infections; therefore JAK-i steroid-sparing effect may be beneficial for patients in long-term treatment

Naphthoquinone Derivatives Exert Their Antitrypanosomal Activity via a Multi-Target Mechanism

BACKGROUND AND METHODOLOGY: Recently, we reported on a new class of naphthoquinone derivatives showing a promising anti-trypanosomatid profile in cell-based experiments. The lead of this series (B6, 2-phenoxy-1,4-naphthoquinone) showed an ED(50) of 80 nM against Trypanosoma brucei rhodesiense, and a selectivity index of 74 with respect to mammalian cells. A multitarget profile for this compound is easily conceivable, because quinones, as natural products, serve plants as potent defense chemicals with an intrinsic multifunctional mechanism of action. To disclose such a multitarget profile of B6, we exploited a chemical proteomics approach. PRINCIPAL FINDINGS: A functionalized congener of B6 was immobilized on a solid matrix and used to isolate target proteins from Trypanosoma brucei lysates. Mass analysis delivered two enzymes, i.e. glycosomal glycerol kinase and glycosomal glyceraldehyde-3-phosphate dehydrogenase, as potential molecular targets for B6. Both enzymes were recombinantly expressed and purified, and used for chemical validation. Indeed, B6 was able to inhibit both enzymes with IC(50) values in the micromolar range. The multifunctional profile was further characterized in experiments using permeabilized Trypanosoma brucei cells and mitochondrial cell fractions. It turned out that B6 was also able to generate oxygen radicals, a mechanism that may additionally contribute to its observed potent trypanocidal activity. CONCLUSIONS AND SIGNIFICANCE: Overall, B6 showed a multitarget mechanism of action, which provides a molecular explanation of its promising anti-trypanosomatid activity. Furthermore, the forward chemical genetics approach here applied may be viable in the molecular characterization of novel multitarget ligands

Psychosocial assessment of families caring for a child with acute lymphoblastic leukemia, epilepsy or asthma: Psychosocial risk as network of interacting symptoms

The purpose of this study is to assess psychosocial risk across several pediatric medical conditions and test the hypothesis that different severe or chronic pediatric illnesses are characterized by disease specific enhanced psychosocial risk and that risk is driven by disease specific connectivity and interdependencies among various domains of psychosocial function using the Psychosocial Assessment Tool (PAT). In a multicenter prospective cohort study of 195 patients, aged 5-12, 90 diagnosed with acute lymphoblastic leukemia (ALL), 42 with epilepsy and 63 with asthma, parents completed the PAT2.0 or the PAT2.0 generic version. Multivariate analysis was performed with disease as factor and age as covariate. Graph theory and network analysis was employed to study the connectivity and interdependencies among subscales of the PAT while data-driven cluster analysis was used to test whether common patterns of risk exist among the various diseases. Using a network modelling approach analysis, we observed unique patterns of interconnected domains of psychosocial factors. Each pathology was characterized by different interdependencies among the most central and most connected domains. Furthermore, data-driven cluster analysis resulted in two clusters: Patients with ALL (89%) mostly belonged to cluster 1, while patients with epilepsy and asthma belonged primarily to cluster 2 (83% and 82% respectively). In sum, implementing a network approach improves our comprehension concerning the character of the problems central to the development of psychosocial difficulties. Therapy directed at problems related to the most central domain(s) constitutes the more rational one because such an approach will inevitably carry over to other domains that depend on the more central function

Pediatric tuberculosis in Italian children: Epidemiological and clinical data from the Italian register of pediatric tuberculosis

Tuberculosis (TB) is one of the leading causes of death worldwide. Over the last decades, TB has also emerged in the pediatric population. Epidemiologic data of childhood TB are still limited and there is an urgent need of more data on very large cohorts. A multicenter study was conducted in 27 pediatric hospitals, pediatric wards, and public health centers in Italy using a standardized form, covering the period of time between 1 January 2010 and 31 December 2012. Children with active TB, latent TB, and those recently exposed to TB or recently adopted/immigrated from a high TB incidence country were enrolled. Overall, 4234 children were included; 554 (13.1%) children had active TB, 594 (14.0%) latent TB and 3086 (72.9%) were uninfected. Among children with active TB, 481 (86.8%) patients had pulmonary TB. The treatment of active TB cases was known for 96.4% (n = 534) of the cases. Overall, 210 (39.3%) out of these 534 children were treated with three and 216 (40.4%) with four first-line drugs. Second-line drugs where used in 87 (16.3%) children with active TB. Drug-resistant strains of Mycobacterium tuberculosis were reported in 39 (7%) children. Improving the surveillance of childhood TB is important for public health care workers and pediatricians. A non-negligible proportion of children had drug-resistant TB and was treated with second-line drugs, most of which are off-label in the pediatric age. Future efforts should concentrate on improving active surveillance, diagnostic tools, and the availability of antitubercular pediatric formulations, also in low-endemic countries